J Cancer 2019; 10(18):4165-4177. doi:10.7150/jca.33497

Research Paper

iTRAQ-based Comparative Serum Proteomic Analysis of Prostate Cancer Patients with or without Bone Metastasis

Bo Yan1,2, Binshen Chen1, Shaoju Min3, Yubo Gao1, Yiming Zhang1, Peng Xu1, Chaoming Li1, Jiasheng Chen1, Guangheng Luo2, Chunxiao Liu1✉

1. Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
2. Department of Urology, Guizhou Provincial People's Hospital, Medical College of Guizhou University, Guiyang, Guizhou, China
3. Department of Clinical Laboratory, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

Abstract

Background: Once prostate cancer developed bone metastasis, the quality of life and prognosis of patients are seriously affected as no effective treatment is currently available. It is necessary to explore the mechanism of bone metastasis and new therapeutic targets.

Purpose: To find out the differentially expressed serum proteins in prostate cancer patients with bone metastasis and analyze the expression of key proteins in prostate cancer tissues, serum and prostate cancer cell lines. So as to provide a basis for revealing the mechanism of bone metastasis and designing new therapeutic targets.

Methods: iTRAQ-based proteomics method was used to compare serum differential proteins in prostate cancer patients with and without bone metastasis. Three key proteins (CD59, haptoglobin and tetranectin) which had significant fold changes were selected to validate the results of mass spectrometry. Immunohistochemistry and ELISA were applied to tissues and serum samples from prostate cancer patients, respectively, for validation. Finally, western blot, flow cytometry, and immunocytochemistry were used to analyze the expression of the three differentially expressed proteins in the prostate cancer cell lines PC3, LNCap, and Du145.

Results: Thirty-two differentially expressed proteins related to bone metastasis of prostate cancer were identified, of which 11 were up-regulated and 21 were down-regulated. CD59 and haptoglobin were up-regulated in prostate cancer with bone metastasis while tetranectin was down-regulated. Tetranectin showed differential expression in epithelial and stromal cells of prostate cancer and hyperplasia tissues.The expression of CD59 was highest in PC3 and lowest in LNCap, while the expression of haptoglobin and tetranectin was the highest in DU145 and lowest in PC3.

Conclusion: Mass spectrometry analysis showed that there were more differentially expressed proteins in the serum of patients with bone metastasis than those without metastasis. It has been verified that CD59, haptoglobin and tetranectin are prostate cancer bone metastasis related proteins.

Keywords: prostate cancer, bone metastasis, quantitative proteomics, iTRAQ labeling

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How to cite this article:
Yan B, Chen B, Min S, Gao Y, Zhang Y, Xu P, Li C, Chen J, Luo G, Liu C. iTRAQ-based Comparative Serum Proteomic Analysis of Prostate Cancer Patients with or without Bone Metastasis. J Cancer 2019; 10(18):4165-4177. doi:10.7150/jca.33497. Available from http://www.jcancer.org/v10p4165.htm